Phase I The primary objective of the SBR effort proposed herein is to investigate the feasibility of significantly enhancing the imaging capacity of diffuse optical tomography (DOT) technology by using a novel 3D image device to provide accurate three-dimensional (3D) geometric boundary conditions in non-contact-detection "3D DOT" systems. The 3D surface image also facilitates the DOT systems in multi-spectral image registration. A prototype of the novel 3D DOT system will be built in Phase2 program that integrates both 2D and 3D image function into single sensor unit, and provide four-channel multi-spectral imaging capability for in vivo diffuse optical tomography imaging applications. DOT in the near-infrared (NIR) has re-emerged as a promising imaging modality and dramatically improved our ability to localize and qualify tissue structures with light. However, the advanced DOT algorithm requires good knowledge of the boundary geometry of the diffuse medium imaged in order to provide accurate forward models of light propagation within this medium. Original experimental DOT demonstrations for reconstructing absorbers, scatterers and fluorochromes all used phantoms or tissues confined to easily modeled geometries such as a slab or a cylinder. In recent years several methods have been developed to model photon propagation through diffuse media with complex boundaries using Monte Carlo approaches, finite solutions of the diffusion or transport equation or more recently analytical methods based on the tangent-plane method. To fully exploit the advantages to these sophisticated algorithms, accurate 3D boundary geometry of the subject has to be extracted in practical, real-time, and in vivo manner. To date, there is no known reported technique for extracting 3D dimensional boundaries with fully automated, accurate and real-time in vivo performance. We propose this SBIR project to address this need. The long-team goal of this research project is to develop a new optical tomography system that coherently combines the diffuse optical tomographic sensor/light source with real-time precision 3D surface images device so that the boundary geometry of the object to be imaged would be extracted almost simultaneously as the diffuse optical tomography imaging is performing. Specifically, our Phase 1 technical aims are listed below: Aim#1: Develop 3D imaging technique that is suitable for in vivo automatic real-time surface imaging of small animals. Aim#2: Develop new algorithms for DOT imaging that are able to utilize the precise 3D geometric boundary data. Aim#3: Build a prototype system that integrates the 3D camera with DOT imaging device. Aim#4: Perform experiments to demonstrate the quantitative enhancement of spatial resolution and accuracy. Aim#5: Prepare for Phase 2 work plan. Phase II The primary objective of the SBIR effort proposed herein is to investigate the feasibility of significantly enhancing the imaging capacity and accuracy of diffuse optical tomography (DOT) technology by using a novel 3D surface imaging device that extracts accurate three-dimensional (3D) geometric boundaries and high-density detection array. Phase 2 of this proposal concentrates in a) integrating the DOT measurements with the 3D boundary extraction in a single imaging modality, in b) accurately co-registering the DOT measurements with the underlying boundary, in c) improving the source illumination characteristics and d) implementing multi-spectral imaging capabilities for simultaneously targeting multiple chromophores or fluorochromes. The developments in imaging technology to be developed under the Phase 2 SBIR project offers the following distinct advantages: * The newly added capability to automatically and in-vivo acquire accurate 3D surface profiles. * Enhancement of DOT imaging and quantification capacity by incorporating photon detection with very accurate positional accuracy. * Enhanced ability to perform multi-spectral imaging by using advanced source and detection technology. * Higher spatial resolution and measurement information content; the proposed 3D-DOT system design utilizes a cooled CCD sensor (512 x 512 pixels or more), instead of limited number of optical fiber probes (typically about 32 channels), to collect the optical measurement from the subject. * Efficiency and user friendliness in handling DOT imaging procedures. * We herein proposed a three-year Phase 2 research and development project that focuses on three aims: Aim #1 (main activity in year 1): Design, build and test a prototype of the integrated 2D/3D DOT system; Aim #2 (main activity in year 2): Design, build and test a prototype of the multi-spectral 3D DOT system; Aim #3 (main activity in year 3): Perform extensive tests on phantoms and animals to evaluate quantitative performance of the integrated multi-spectral 3D DOT system.